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Auditory perception requires categorizing sound sequences, such as speech, into classes, such as syllables. Such categorization depends not only on the sequences’ acoustic waveform, but also on the listener’s sensory uncertainty, any individual sound’s relevance to the task, and learning the temporal statistics of the acoustic environment. Although previous studies have explored the effects of these perceptual and cognitive factors in separation, whether and how their interplay shapes categorization is unknown. Here, we tested this interplay by measuring human participants’ performance on a multi-tone categorization task. Using a Bayesian framework, we found that task-relevant tones contributed more to category choice than task-irrelevant tones, confirming that participants combined information about sensory features with task relevance. Conversely, poor estimates of tones’ task relevance or high sensory uncertainty adversely impacted category choice. Learning temporal statistics of sound category also affected decisions – the magnitude of this effect correlated inversely with participants’ relevance estimates. These results demonstrate that humans differentially weigh sensory uncertainty, task relevance and statistical learning, providing a novel understanding of sensory decision-making under real-life behavioral demands.

Monoclonal B-cell lymphocytosis (MBL) is a precursor to CLL. Other than age, sex, and CLL family-history, little is known about factors associated with MBL risk. A polygenic-risk-score (PRS) of 41 CLL-susceptibility variants has been found to be associated with CLL risk among individuals of European-ancestry(EA). Here, we evaluate these variants, the PRS, and environmental factors for MBL risk. We also evaluate these variants and the CLL-PRS among African-American (AA) and EA-CLL cases and controls. Our study included 560 EA MBLs, 869 CLLs (696 EA/173 AA), and 2866 controls (2631 EA/235 AA). We used logistic regression, adjusting for age and sex, to estimate odds ratios (OR) and 95% confidence intervals within each race. We found significant associations with MBL risk among 21 of 41 variants and with the CLL-PRS (OR = 1.86, P = 1.9 × 10-29, c-statistic = 0.72). Little evidence of any association between MBL risk and environmental factors was observed. We observed significant associations of the CLL-PRS with EA-CLL risk (OR = 2.53, P = 4.0 × 10-63, c-statistic = 0.77) and AA-CLL risk (OR = 1.76, P = 5.1 × 10-5, c-statistic = 0.62). Inherited genetic factors and not environmental are associated with MBL risk. In particular, the CLL-PRS is a strong predictor for both risk of MBL and EA-CLL, but less so for AA-CLL supporting the need for further work in this population.

Multisensory processing often has facilitation and/or interference effects (Chen & Spence, 2010; Thomas et al., 2017) yet the mechanisms remain unclear. This experiment used a Stroop-like task (Stroop, 1935) to examine how congruent, incongruent, and irrelevant information presented in one sensory modality affects processing and responding in a different modality (see Figure 1 for trial types). Participants were simultaneously presented with pictures and sounds of animals or vehicles. In separate blocks they had to respond to either the visual or auditory stimulus, while ignoring the other modality. Results suggest that visual stimuli have a larger effect on auditory responding than vice versa. Incongruent visual stimuli had a larger effect on accuracy while congruent visual stimuli had a larger impact on response time. We will present additional data at the poster focusing on factors that may affect congruency effects including individual differences and types of auditory stimuli.

Cortical responses to sensory stimuli are strongly modulated by temporal context. One of the best studied examples of such modulation is sensory adaptation. We first show that in response to repeated tones pyramidal (Pyr) neurons in male mouse auditory cortex (A1) exhibit facilitating and stable responses, in addition to adapting responses. To examine the potential mechanisms underlying these distinct temporal profiles, we developed a reduced spiking model of sensory cortical circuits that incorporated the signature short-term synaptic plasticity (STP) profiles of the inhibitory parvalbumin (PV) and somatostatin (SST) interneurons. The model accounted for all three temporal response profiles as the result of dynamic changes in excitatory/inhibitory balance produced by STP, primarily through shifts in the relative latency of Pyr and inhibitory neurons. Transition between the three response profiles was possible by changing the strength of the inhibitory PV→Pyr and SST→Pyr synapses. The model predicted that a unit's latency would be related to its temporal profile. Consistent with this prediction, the latency of stable units was significantly shorter than that of adapting and facilitating units. Furthermore, because of the history-dependence of STP the model generated a paradoxical prediction: that inactivation of inhibitory neurons during one tone would decrease the response of A1 neurons to a subsequent tone. Indeed, we observed that optogenetic inactivation of PV neurons during one tone counterintuitively decreased the spiking of Pyr neurons to a subsequent tone 400 ms later. These results provide evidence that STP is critical to temporal context-dependent responses in the sensory cortex.SIGNIFICANCE STATEMENT Our perception of speech and music depends strongly on temporal context, i.e., the significance of a stimulus depends on the preceding stimuli. Complementary neural mechanisms are needed to sometimes ignore repetitive stimuli (e.g., the tic of a clock) or detect meaningful repetition (e.g., consecutive tones in Morse code). We modeled a neural circuit that accounts for diverse experimentally-observed response profiles in auditory cortex (A1) neurons, based on known forms of short-term synaptic plasticity (STP). Whether the simulated circuit reduced, maintained, or enhanced its response to repeated tones depended on the relative dominance of two different types of inhibitory cells. The model made novel predictions that were experimentally validated. Results define an important role for STP in temporal context-dependent perception.

The golden jackal of Africa (Canis aureus) has long been considered a conspecific of jackals distributed throughout Eurasia, with the nearest source populations in the Middle East. However, two recent reports found that mitochondrial haplotypes of some African golden jackals aligned more closely to gray wolves (Canis lupus) [1, 2], which is surprising given the absence of gray wolves in Africa and the phenotypic divergence between the two species. Moreover, these results imply the existence of a previously unrecognized phylogenetically distinct species despite a long history of taxonomic work on African canids. To test the distinct-species hypothesis and understand the evolutionary history that would account for this puzzling result, we analyzed extensive genomic data including mitochondrial genome sequences, sequences from 20 autosomal loci (17 introns and 3 exon segments), microsatellite loci, X- and Y-linked zinc-finger protein gene (ZFX and ZFY) sequences, and whole-genome nuclear sequences in African and Eurasian golden jackals and gray wolves. Our results provide consistent and robust evidence that populations of golden jackals from Africa and Eurasia represent distinct monophyletic lineages separated for more than one million years, sufficient to merit formal recognition as different species: C. anthus (African golden wolf) and C. aureus (Eurasian golden jackal). Using morphologic data, we demonstrate a striking morphologic similarity between East African and Eurasian golden jackals, suggesting parallelism, which may have misled taxonomists and likely reflects uniquely intense interspecific competition in the East African carnivore guild. Our study shows how ecology can confound taxonomy if interspecific competition constrains size diversification.

The golden jackal of Africa (Canis aureus) has long been considered a conspecific of jackals distributed throughout Eurasia, with the nearest source populations in the Middle East. However, two recent reports found that mitochondrial haplotypes of some African golden jackals aligned more closely to gray wolves (Canis lupus), which is surprising given the absence of gray wolves in Africa and the phenotypic divergence between the two species. Moreover, these results imply the existence of a previously unrecognized phylogenetically distinct species despite a long history of taxonomic work on African canids. To test the distinct-species hypothesis and understand the evolutionary history that would account for this puzzling result, we analyzed extensive genomic data including mitochondrial genome sequences, sequences from 20 autosomal loci (17 introns and 3 exon segments), microsatellite loci, X- and Y-linked zinc-finger protein gene (ZFX and ZFY) sequences, and whole-genome nuclear sequences in African and Eurasian golden jackals and gray wolves. Our results provide consistent and robust evidence that populations of golden jackals from Africa and Eurasia represent distinct monophyletic lineages separated for more than one million years, sufficient to merit formal recognition as different species: C. anthus (African golden wolf) and C. aureus (Eurasian golden jackal). Using morphologic data, we demonstrate a striking morphologic similarity between East African and Eurasian golden jackals, suggesting parallelism, which may have misled taxonomists and likely reflects uniquely intense interspecific competition in the East African carnivore guild. Our study shows how ecology can confound taxonomy if interspecific competition constrains size diversification.

The golden jackal of Africa (Canis aureus) has long been considered a conspecific of jackals distributed throughout Eurasia, with the nearest source populations in the Middle East. However, two recent reports found that mitochondrial haplotypes of some African golden jackals aligned more closely to gray wolves (Canis lupus), which is surprising given the absence of gray wolves in Africa and the phenotypic divergence between the two species. Moreover, these results imply the existence of a previously unrecognized phylogenetically distinct species despite a long history of taxonomic work on African canids. To test the distinct-species hypothesis and understand the evolutionary history that would account for this puzzling result, we analyzed extensive genomic data including mitochondrial genome sequences, sequences from 20 autosomal loci (17 introns and 3 exon segments), microsatellite loci, X- and Y-linked zinc-finger protein gene (ZFX and ZFY) sequences, and whole-genome nuclear sequences in African and Eurasian golden jackals and gray wolves. Our results provide consistent and robust evidence that populations of golden jackals from Africa and Eurasia represent distinct monophyletic lineages separated for more than one million years, sufficient to merit formal recognition as different species: C. anthus (African golden wolf) and C. aureus (Eurasian golden jackal). Using morphologic data, we demonstrate a striking morphologic similarity between East African and Eurasian golden jackals, suggesting parallelism, which may have misled taxonomists and likely reflects uniquely intense interspecific competition in the East African carnivore guild. Our study shows how ecology can confound taxonomy if interspecific competition constrains size diversification.

We have previously shown that multidrug-resistant cancer cells display elevated levels of glucosylceramide (Lavie, Y., Cao, H., Bursten, S. L., Giuliano, A. E., and Cabot, M. C. (1996) J. Biol. Chem. 271, 19530-19536). In this study we used the multidrug-resistant human breast cancer cell line MCF-7-Adriamycin-resistant (AdrR), which exhibits marked accumulation of glucosylceramide compared with the parental MCF-7 wild type (drug-sensitive) cell line, to define the relationship between glycolipids and multidrug resistance (MDR). Herein it is shown that clinically relevant concentrations of tamoxifen, verapamil, and cyclosporin A, all circumventors of MDR, markedly decrease glucosylceramide levels in MCF-7-AdrR cells (IC50 values, 1. 0, 0.8, and 2.3 microM, respectively). In intact cells, tamoxifen inhibited glycosphingolipid synthesis at the step of ceramide glycosylation. In cell-free assays for glucosylceramide synthase, tamoxifen (1:10 molar ratio with ceramide) inhibited glucosylceramide formation by nearly 50%. In cell cultures, inhibition of glucosylceramide synthesis by tamoxifen is correlated with its ability to sensitize MCF-7-AdrR cells to Adriamycin toxicity. Moreover, treatment of cells with 1-phenyl-2-palmitoylamino-3-morpholino-1-propanol, an inhibitor of glucosylceramide synthesis, likewise sensitized MCF-7-AdrR cells to Adriamycin. It is concluded that high cellular levels of glucosylceramide are correlated with MDR, and that glycolipids are a target for the action of MDR-reversing agents such as tamoxifen. The data entertain the notion that drug resistance phenomena are aligned with cell capacity to metabolize ceramide.

The capacity of the two cerebral hemispheres for temporal processing was investigated in two experiments concerned with sensory and motor processing, respectively. The temporal processing of sensory information was examined in a task requiring simultaneity judgement of pairs of tactile stimuli delivered unimanually or bimanually. Unimanual stimulation permitted presentation of both events to the same hemisphere while bimanual stimulation involved both hemispheres and necessarily required interhemispheric communication to compare stimulus onset asynchrony (SOA). The order of presentation of asynchronous pairs determined which cerebral hemisphere was activated first. Pairs of stimuli were judged as simultaneous at longer SOAs in the bimanual than the unimanual conditions whilst unimanual left and right simultaneity thresholds did not differ. These results suggest that the two hemispheres are equally capable of temporally resolving a pair of simple tactile stimuli. A structural model proposing that temporal comparisons are carried out in the hemisphere receiving the second stimulus provides the best account of the results.The temporal processing of motor information was examined in a task requiring the planning and execution of sequences of finger movements. A predetermined number of double-tap responses with the index and middle fingers of a given hand were required in response to a visual cue in the ipsilateral visual field. The restriction of the performance cue in each trial to the hemisphere controlling the response permitted assessment of the contribution of each cerebral hemisphere to differences in hand skill. Movement time increased linearly for both hands with increasing length of tap sequence and did not differentiate hand performance. Response preparation time, however, increased linearly with increasing task load for the preferred hand but varied quadratically for the non-preferred hand. These results indicate that differences in hand skill may be determined by the mode of response preparation within the contralateral hemisphere. They also suggest that studies of hand differences involving fixed levels of motor demand would not properly differentiate hand performance.Together, these studies indicate that both cerebral hemispheres are capable of the temporal processing of sensory and motor information but that the hemisphere primarily involved is determined by side of stimulus or response, respectively.